A systematic mapping review of clinical guidelines for the management of fatigue in long-term physical health conditions.

PURPOSE: Despite a high prevalence of fatigue and its importance to patients, many people with long-term conditions do not receive fatigue management as part of their treatment. This review is aimed to identify clinical guidance for the management of fatigue in long-term physical health conditions. METHODS: A systematic mapping review was conducted in accordance with Social Care Institute for Excellence systematic review guidance. Bibliographic databases and guideline repositories were searched for clinical guidelines for long-term conditions, published between January 2008 and July 2018, with a search for updates conducted in May 2023. Data were extracted on the recommendations made for managing fatigue and, where cited, the underlying research evidence used to support these recommendations was also extracted. RESULTS: The review included 221 guidelines on 67 different long-term conditions. Only 30 (13.6%) of the guidelines contained recommendations for managing fatigue. These were categorised as clinical (e.g. conduct further investigations), pharmacological, behavioural (e.g. physical activity), psychological, nutritional, complementary, environmental, and multicomponent. The guidelines rated much of the evidence for fatigue management as fairly low quality, highlighting the need to develop and test fatigue-management strategies in high-quality trials. CONCLUSION: This review highlights that management of fatigue is a very important neglected area in the clinical guidelines for managing long-term conditions.

Fatigue is a common and debilitating symptom of many long-term physical health conditions; however, many people do not receive treatment for fatigue.This mapping review found that very few clinical guidelines contain recommendations for managing fatigue, even where published evidence exists.It is essential that developers of clinical guidelines address this important neglected area.

Characterising long COVID: a living systematic review.

BACKGROUND: While it is now apparent clinical sequelae (long COVID) may persist after acute COVID-19, their nature, frequency and aetiology are poorly characterised. This study aims to regularly synthesise evidence on long COVID characteristics, to help inform clinical management, rehabilitation strategies and interventional studies to improve long-term outcomes. METHODS: A living systematic review. Medline, CINAHL (EBSCO), Global Health (Ovid), WHO Global Research on COVID-19 database, LitCovid and Google Scholar were searched till 17 March 2021. Studies including at least 100 people with confirmed or clinically suspected COVID-19 at 12 weeks or more post onset were included. Risk of bias was assessed using the tool produced by Hoy et al. Results were analysed using descriptive statistics and meta-analyses to estimate prevalence. RESULTS: A total of 39 studies were included: 32 cohort, 6 cross-sectional and 1 case-control. Most showed high or moderate risk of bias. None were set in low-income countries and few included children. Studies reported on 10 951 people (48% female) in 12 countries. Most included previously hospitalised people (78%, 8520/10 951). The longest mean follow-up time was 221.7 (SD: 10.9) days post COVID-19 onset. Over 60 physical and psychological signs and symptoms with wide prevalence were reported, most commonly weakness (41%; 95% CI 25% to 59%), general malaise (33%; 95% CI 15% to 57%), fatigue (31%; 95% CI 24% to 39%), concentration impairment (26%; 95% CI 21% to 32%) and breathlessness (25%; 95% CI 18% to 34%). 37% (95% CI 18% to 60%) of patients reported reduced quality of life; 26% (10/39) of studies presented evidence of reduced pulmonary function. CONCLUSION: Long COVID is a complex condition with prolonged heterogeneous symptoms. The nature of studies precludes a precise case definition or risk evaluation. There is an urgent need for prospective, robust, standardised, controlled studies into aetiology, risk factors and biomarkers to characterise long COVID in different at-risk populations and settings. PROSPERO REGISTRATION NUMBER: CRD42020211131.

Mobile Health for Pediatric Weight Management: Systematic Scoping Review.

BACKGROUND: The prevalence and consequences of obesity among children and adolescents remain a leading global public health concern, and evidence-based, multidisciplinary lifestyle interventions are the cornerstone of treatment. Mobile electronic devices are widely used across socioeconomic categories and may provide a means of extending the reach and efficiency of health care interventions. OBJECTIVE: We aimed to synthesize the evidence regarding mobile health (mHealth) for the treatment of childhood overweight and obesity to map the breadth and nature of the literature in this field and describe the characteristics of published studies. METHODS: We conducted a systematic scoping review in line with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses extension for scoping reviews, by searching nine academic databases in addition to gray literature for studies describing acceptability, usability, feasibility, effectiveness, adherence, or cost-effectiveness of interventions assessing mHealth for childhood obesity treatment. We also hand searched the reference lists of relevant articles. Studies aimed at the prevention of overweight or obesity were excluded, as were studies in which mHealth was not the primary mode of treatment delivery for at least one study arm or was not independently assessed. A random portion of all abstracts and full texts was double screened by a second reviewer to ensure consistency. Data were charted according to study characteristics, including design, participants, intervention content, behavior change theory (BCT) underpinning the study, mode of delivery, and outcomes measured. RESULTS: We identified 42 eligible studies assessing acceptability (n=7), usability (n=2), feasibility or pilot studies (n=15), treatment effect (n=17), and fidelity (n=1). Change in BMI z-scores or percentiles was most commonly measured, among a variety of dietary, physical activity, psychological, and usability or acceptability measures. SMS, mobile apps, and wearable devices made up the majority of mobile interventions, and 69% (29/42) of the studies specified a BCT used. CONCLUSIONS: Pediatric weight management using mHealth is an emerging field, with most work to date aimed at developing and piloting such interventions. Few large trials are published, and these are heterogeneous in nature and rarely reported according to the Consolidated Standards of Reporting Trials for eHealth guidelines. There is an evidence gap in the cost-effectiveness analyses of such studies.

What are the long-term symptoms and complications of COVID-19: a protocol for a living systematic review.

Although the majority of patients with COVID-19 will experience mild to moderate symptoms and will recover fully, there is now increasing evidence that a significant proportion will experience persistent symptoms for weeks or months after the acute phase of the illness. These symptoms include, among others, fatigue, problems in breathing, lack of smell and taste, headaches, and also depression and anxiety. It has also become clear that the virus has lasting effects not only on the respiratory system but also on other parts of the body, including the heart, liver, and the nervous system. In this paper we present a protocol for a living systematic review that aims to synthesize the evidence on the prevalence and duration of symptoms and clinical features of post-acute COVID-19 and its long-term complications. The living systematic review will be updated regularly, initially monthly with update cycles under continuous review as the pace of new evidence generated develops through the pandemic. We will include studies that follow up with COVID-19 patients who have experienced persistent mild, moderate or severe symptoms, with no restrictions regarding country, setting, or language. We will use descriptive statistics to analyse the data and our findings will be presented as infographics to facilitate transcription to lay audiences. Ultimately, we aim to support the work of policy makers, practitioners, and patients when planning rehabilitation for those recovering from COVID-19. The protocol has been registered with PROSPERO ( CRD42020211131, 25/09/2020).

The Impact of Using Emotionally Arousing Stimuli on Muscle Response Testing Accuracy.

INTRODUCTION: Muscle response testing (MRT) is an assessment method used by 1 million practitioners worldwide, yet its usefulness remains uncertain. The aim of this study, one in a series assessing the accuracy of MRT, was to determine whether emotionally arousing stimuli influence its accuracy compared to neutral stimuli. METHODS: To assess diagnostic test accuracy 20 MRT practitioners were paired with 20 test patients (TPs). Forty MRTs were performed as TPs made true and false statements about emotionally arousing and neutral pictures. Blocks of MRT alternated with blocks of intuitive guessing (IG). RESULTS: MRT accuracy using emotionally arousing stimuli was different than when using neutral stimuli. However, MRT accuracy was found to be significantly better than IG and chance. Similar to previous studies in this series, this study failed to detect any characteristic that consistently influenced MRT accuracy. CONCLUSION: Using emotionally arousing stimuli had no effect on MRT accuracy compared to using neutral stimuli. This study would have been strengthened by adding personally relevant lies instead of impersonal stimuli. A limitation of this study is its lack of generalizability to other applications of MRT. This study shows that a simple yet robust methodology for assessing MRT as a diagnostic tool can be implemented effectively.

SMOOTH: Self-Management of Open Online Trials in Health analysis found improvements were needed for reporting methods of internet-based trials.

BACKGROUND AND OBJECTIVES: The growth of trials conducted over the internet has increased, but with little practical guidance for their conduct, and it is sometimes challenging for researchers to adapt the conventions used in face-to-face trials and maintain the validity of the work. The aim of the study is to systematically explore existing self-recruited online randomized trials of self-management interventions and analyze the trials to assess their strengths and weaknesses, the quality of reporting, and the involvement of lay persons as collaborators in the research process. STUDY DESIGN AND SETTINGS: The Online Randomized Controlled Trials of Health Information Database was used as the sampling frame to identify a subset of self-recruited online trials of self-management interventions. The authors cataloged what these online trials were assessing, appraised study quality, extracted information on how trials were run, and assessed the potential for bias. We searched out how public and patient participation was integrated into online trial design and how this was reported. We recorded patterns of use for registration, reporting, settings, informed consent, public involvement, supplementary materials, and dissemination planning. RESULTS: The sample included 41 online trials published from 2002 to 2015. The barriers to replicability and risk of bias in online trials included inadequate reporting of blinding in 28/41 (68%) studies; high attrition rates with incomplete or unreported data in 30/41 (73%) of trials; and 26/41 (63%) of studies were at high risk for selection bias as trial registrations were unreported. The methods for (23/41, 56%) trials contained insufficient information to replicate the trial, 19/41 did not report piloting the intervention. Only 2/41 studies were cross-platform compatible. Public involvement was most common for advisory roles (n = 9, 22%), and in the design, usability testing, and piloting of user materials (n = 9, 22%). CONCLUSION: This study catalogs the state of online trials of self-management in the early 21st century and provides insights for online trials development as early as the protocol planning stage. Reporting of trials was generally poor and, in addition to recommending that authors report their trials in accordance with CONSORT guidelines, we make recommendations for researchers writing protocols, reporting on and evaluating online trials. The research highlights considerable room for improvement in trial registration, reporting of methods, data management plans, and public and patient involvement in self-recruited online trials of self-management interventions.

What utility scores do mental health service users, healthcare professionals and members of the general public attribute to different health states? A co-produced mixed methods online survey.

BACKGROUND: Utility scores are integral to health economics decision-making. Typically, utility scores have not been scored or developed with mental health service users. The aims of this study were to i) collaborate with service users to develop descriptions of five mental health states (psychosis, depression, eating disorder, medication side effects and self-harm); ii) explore feasibility and acceptability of using scenario-based health states in an e-survey; iii) evaluate which utility measures (standard gamble (SG), time trade off (TTO) and rating scale (RS)) are preferred; and iv) determine how different participant groups discriminate between the health scenarios and rank them. DESIGN AND METHODS: This was a co-produced mixed methods cross-sectional online survey. Utility scores were generated using the SG, TTO and RS methods; difficulty of the completing each method, markers of acceptability and participants' preference were also assessed. RESULTS: A total of 119 participants (58%) fully completed the survey. For any given health state, SG consistently generated higher utility scores compared to RS and for some health states higher also than TTO (i.e. SG produces inflated utility scores relative to RS and TTO). Results suggest that different utility measures produce different evaluations of described health states. The TTO was preferred by all participant groups over the SG. The three participant groups scored four (of five) health scenarios comparably. Psychosis scored as the worst health state to live with while medication side-effects were viewed more positively than other scenarios (depression, eating disorders, self-harm) by all participant groups. However, there was a difference in how the depression scenario was scored, with service users giving depression a lower utility score compared to other groups. CONCLUSION: Mental health state scenarios used to generate utility scores can be co-produced and are well received by a broad range of participants. Utility valuations using SG, TTO and RS were feasible for use with service users, carers, healthcare professionals and members of the general public. Future studies of utility scores in psychiatry should aim to include mental health service users as both co-investigators and respondents.

Heparin versus 0.9% sodium chloride locking for prevention of occlusion in central venous catheters in adults.

BACKGROUND: Intermittent locking of central venous catheters (CVCs) is undertaken to help maintain their patency. There are systematic variations in care: some practitioners use heparin (at different concentrations), whilst others use 0.9% NaCl (normal saline). This review looks at the effectiveness and safety of intermittent locking with heparin compared to 0.9% NaCl to see if the evidence establishes whether one is better than the other. This work is an update of a review first published in 2014. OBJECTIVES: To assess the effectiveness and safety of intermittent locking of CVCs with heparin versus normal saline (NS) in adults to prevent occlusion. SEARCH METHODS: The Cochrane Vascular Information Specialist (CIS) searched the Specialised Register (last searched 11 June 2018) and the Cochrane Central Register of Controlled Trials (CENTRAL; 2018, Issue 5). Searches were also carried out in MEDLINE, Embase, CINAHL, and clinical trials databases (11 June 2018). SELECTION CRITERIA: We included randomised controlled trials in adults ≥ 18 years of age with a CVC that compared intermittent locking with heparin at any concentration versus NS. We applied no restriction on language. DATA COLLECTION AND ANALYSIS: Two review authors independently selected trials, assessed quality, and extracted data. We contacted trial authors to retrieve additional information, when necessary. We carried out statistical analysis using Review Manager 5 and assessed the overall quality of the evidence supporting assessed outcomes using GRADE. We carried out prespecified subgroup analysis. MAIN RESULTS: We identified five new studies for this update (six prior studies were included in the original review), bringing the number of eligible studies to 11, with a total of 2392 participants. We noted differences in methods used by the included studies and variation in heparin concentrations (10 to 5000 IU/mL), time to follow-up (1 to 251.8 days), and the unit of analysis used (participant, catheter, line access).Combined results from these studies showed fewer occlusions with heparin than with NS (risk ratio (RR) 0.70, 95% confidence interval (CI) 0.51 to 0.95; P = 0.02; 1672 participants; 1025 catheters from 10 studies; I² = 14%) and provided very low-quality evidence.We carried out subgroup analysis by unit of analysis (testing for subgroup differences (P = 0.23; I² = 30.3%). When the unit of analysis was the participant, results show no clear differences in all occlusions between heparin and NS (RR 0.79, 95% CI 0.58 to 1.08; P = 0.15; 1672 participants; seven studies). Subgroup analysis using the catheter as the unit of analysis shows fewer occlusions with heparin use (RR 0.53, 95% CI 0.29 to 0.95; P = 0.03; 1025 catheters; three studies). When the unit of analysis was line access, results show no clear differences in occlusions between heparin and NS (RR 1.08, 95% CI 0.84 to 1.40; 770 line accesses; one study).We found no clear differences in the duration of catheter patency (mean difference (MD) 0.44 days, 95% CI -0.10 to 0.99; P = 0.11; 1036 participants; 752 catheters; six studies; low-quality evidence).We found no clear evidence of a difference in the following: CVC-related sepsis (RR 0.74, 95% CI 0.03 to 19.54; P = 0.86; 1097 participants; two studies; low-quality evidence); mortality (RR 0.76, 95% CI 0.44 to 1.31; P = 0.33; 1100 participants; three studies; low-quality evidence); haemorrhage at any site (RR 1.32, 95% CI 0.57 to 3.07; P = 0.52; 1245 participants; four studies; moderate-quality evidence); or heparin-induced thrombocytopaenia (RR 0.21, 95% CI 0.01 to 4.27; P = 0.31; 443 participants; three studies; low-quality evidence).The main reasons for downgrading the quality of evidence were unclear allocation concealment, imprecision, and suspicion of publication bias. AUTHORS' CONCLUSIONS: Given the very low quality of the evidence, we are uncertain whether intermittent locking with heparin results in fewer occlusions than intermittent locking with NS. Low-quality evidence suggests that heparin may have little or no effect on catheter patency. Although we found no evidence of differences in safety (sepsis, mortality, or haemorrhage), the combined trials are not powered to detect rare adverse events such as heparin-induced thrombocytopaenia.

Patient and public involvement in the design of clinical trials: An overview of systematic reviews.

BACKGROUND: Funders encourage lay-volunteer inclusion in research. There are controversy and resistance, given concerns of role confusion, exploratory methods, and limited evidence about what value lay-volunteers bring to research. This overview explores these areas. METHODS: Eleven databases were searched without date or language restrictions for systematic reviews of public and patient involvement (PPI) in clinical trials design. This systematic overview of PPI included 27 reviews from which areas of good and bad practice were identified. Strengths, weaknesses, opportunities, and threats of PPI were explored through use of meta-narrative analysis. RESULTS: Inclusion criteria were met by 27 reviews ranging in quality from high (n = 7), medium (n = 14) to low (n = 6) reviews. Reviews were assessed using CERQUAL NICE, CASP for qualitative research and CASP for systematic reviews. Four reviews report risk of bias. Public involvement roles were primarily in agenda setting, steering committees, ethical review, protocol development, and piloting. Research summaries, follow-up, and dissemination contained PPI, with lesser involvement in data collection, analysis, or manuscript authoring. Trialists report difficulty in finding, retaining, and reimbursing volunteers. Respectful inclusion, role recognition, mutual flexibility, advance planning, and sound methods were reported as facilitating public involvement in research. Public involvement was reported to have increased the quantity and quality of patient relevant priorities and outcomes, enrollment, funding, design, implementation, and dissemination. Challenges identified include lack of clarity within common language, roles, and research boundaries, while logistical needs include extra time, training, and funding. Researchers report struggling to report involvement and avoid tokenism. CONCLUSIONS: Involving patients and the public in clinical trials design can be beneficial but requires resources, preparation, training, flexibility, and time. Issues to address include reporting deficits for risk of bias, study quality, and conflicts of interests. We need to address these tensions and improve dissemination strategies to increase PPI and health literacy.

Certolizumab pegol (CDP870) for rheumatoid arthritis in adults.

BACKGROUND: Tumour necrosis factor (TNF)-alpha inhibitors are beneficial for the treatment of rheumatoid arthritis (RA) for reducing the risk of joint damage, improving physical function and improving the quality of life. This review is an update of the 2014 Cochrane Review of the treatment of RA with certolizumab pegol. OBJECTIVES: To assess the clinical benefits and harms of certolizumab pegol (CZP) in people with RA who have not responded well to conventional disease-modifying anti-rheumatic drugs (DMARDs). SEARCH METHODS: We searched the Cochrane Central Register of Controlled Trials (CENTRAL: Cochrane Library 2016, Issue 9), MEDLINE, Embase, Web of Knowledge, reference lists of articles, clinicaltrials.gov and ICTRP of WHO. The searches were updated from 2014 (date of the last search for the previous version) to 26 September 2016. SELECTION CRITERIA: Randomised controlled trials that compared certolizumab pegol with any other agent, including placebo or methotrexate (MTX), in adults with active RA, regardless of current or prior treatment with conventional disease-modifying anti-rheumatic drugs (DMARDs), such as MTX. DATA COLLECTION AND ANALYSIS: Two review authors independently checked search results, extracted data and assessed trial quality. We resolved disagreements by discussion or referral to a third review author. MAIN RESULTS: We included 14 trials in this update, three more than previously. Twelve trials (5422 participants) included measures of benefit. We pooled 11 of them, two more than previously. Thirteen trials included information on harms, (5273 participants). The duration of follow-up varied from 12 to 52 weeks and the range of doses of certolizumab pegol varied from 50 to 400 mg given subcutaneously. In Phase III trials, the comparator was placebo plus MTX in seven trials and placebo in five. In the two Phase II trials the comparator was only placebo.The approved dose of certolizumab pegol, 200 mg every other week, produced clinically important improvements at 24 weeks for the following outcomes:- American College of Rheumatology (ACR) 50% improvement (pain, function and other symptoms of RA): 25% absolute improvement (95% confidence interval (CI) 20% to 33%); number need to treat for an additional beneficial outcome (NNTB) of 4 (95% CI 3 to 5); risk ratio (RR) 3.80 (95% CI 2.42 to 5.95), 1445 participants, 5 studies.- The Health Assessment Questionnaire (HAQ): -12% absolute improvement (95% CI -9% to -14%); NNTB of 8 (95% CI 7 to 11); mean difference (MD) - 0.35 (95% CI -0.43 to -0.26; 1268 participants, 4 studies) (scale 0 to 3; lower scores mean better function).- Proportion of participants achieving remission (Disease Activity Score (DAS) < 2.6) absolute improvement 10% (95% CI 8% to 16%); NNTB of 8 (95% CI 6 to 12); risk ratio (RR) 2.94 (95% CI 1.64 to 5.28), 2420 participants, six studies.- Radiological changes: erosion score (ES) absolute improvement -0.29% (95% CI -0.42% to -0.17%); NNTB of 6 (95% CI 4 to 10); MD -0.67 (95% CI -0.96 to -0.38); 714 participants, two studies (scale 0 to 230), but not a clinically important difference.-Serious adverse events (SAEs) were statistically but not clinically significantly more frequent for certolizumab pegol (200 mg every other week) with an absolute rate difference of 3% (95% CI 1% to 4%); number needed to treat for an additional harmful outcome (NNTH) of 33 (95% CI 25 to 100); Peto odds ratio (OR) 1.47 (95% CI 1.13 to 1.91); 3927 participants, nine studies.There was a clinically significant increase in all withdrawals in the placebo groups (for all doses and at all follow-ups) with an absolute rate difference of -29% (95% CI -16% to -42%), NNTH of 3 (95% CI 2 to 6), RR 0.47 (95% CI 0.39 to 0.56); and there was a clinically significant increase in withdrawals due to adverse events in the certolizumab groups (for all doses and at all follow-ups) with an absolute rate difference of 2% (95% CI 0% to 3%); NNTH of 58 (95% CI 28 to 329); Peto OR 1.45 (95% CI 1.09 to 1.94) 5236 participants Twelve studies.We judged the quality of evidence to be high for ACR50, DAS remission, SAEs and withdrawals due to adverse events, and moderate for HAQ and radiological changes, due to concerns about attrition bias. For all withdrawals we judged the quality of evidence to be moderate, due to inconsistency. AUTHORS' CONCLUSIONS: The results and conclusions did not change from the previous review. There is a moderate to high certainty of evidence from randomised controlled trials that certolizumab pegol, alone or combined with methotrexate, is beneficial in the treatment of RA for improved ACR50 and health-related quality of life, an increased chance of remission of RA, and reduced joint damage as seen on x-ray. Fewer people stopped taking their treatment, but most of these who did stopped due to serious adverse events. Adverse events were more frequent with active treatment. We found a clinically but not statistically significant risk of serious adverse events.

Establishing a library of resources to help people understand key concepts in assessing treatment claims-The "Critical thinking and Appraisal Resource Library" (CARL).

BACKGROUND: People are frequently confronted with untrustworthy claims about the effects of treatments. Uncritical acceptance of these claims can lead to poor, and sometimes dangerous, treatment decisions, and wasted time and money. Resources to help people learn to think critically about treatment claims are scarce, and they are widely scattered. Furthermore, very few learning-resources have been assessed to see if they improve knowledge and behavior. OBJECTIVES: Our objectives were to develop the Critical thinking and Appraisal Resource Library (CARL). This library was to be in the form of a database containing learning resources for those who are responsible for encouraging critical thinking about treatment claims, and was to be made available online. We wished to include resources for groups we identified as 'intermediaries' of knowledge, i.e. teachers of schoolchildren, undergraduates and graduates, for example those teaching evidence-based medicine, or those communicating treatment claims to the public. In selecting resources, we wished to draw particular attention to those resources that had been formally evaluated, for example, by the creators of the resource or independent research groups. METHODS: CARL was populated with learning-resources identified from a variety of sources-two previously developed but unmaintained inventories; systematic reviews of learning-interventions; online and database searches; and recommendations by members of the project group and its advisors. The learning-resources in CARL were organised by 'Key Concepts' needed to judge the trustworthiness of treatment claims, and were made available online by the James Lind Initiative in Testing Treatments interactive (TTi) English (www.testingtreatments.org/category/learning-resources).TTi English also incorporated the database of Key Concepts and the Claim Evaluation Tools developed through the Informed Healthcare Choices (IHC) project (informedhealthchoices.org). RESULTS: We have created a database of resources called CARL, which currently contains over 500 open-access learning-resources in a variety of formats: text, audio, video, webpages, cartoons, and lesson materials. These are aimed primarily at 'Intermediaries', that is, 'teachers', 'communicators', 'advisors', 'researchers', as well as for independent 'learners'. The resources included in CARL are currently accessible at www.testingtreatments.org/category/learning-resources. CONCLUSIONS: We hope that ready access to CARL will help to promote the critical thinking about treatment claims, needed to help improve healthcare choices.

Oxygen therapy for acute myocardial infarction.

BACKGROUND: Oxygen (O2) is widely used in people with acute myocardial infarction (AMI). Previous systematic reviews concluded that there was insufficient evidence to know whether oxygen reduced, increased or had no effect on heart ischaemia or infarct size. Our first Cochrane review in 2010 also concluded there was insufficient evidence to know whether oxygen should be used. Since 2010, the lack of evidence to support this widely used intervention has attracted considerable attention, prompting further trials of oxygen therapy in myocardial infarction patients. It is thus important to update this Cochrane review. OBJECTIVES: To assess the effects of routine use of inhaled oxygen for acute myocardial infarction (AMI). SEARCH METHODS: We searched the following bibliographic databases on 6 June 2015: the Cochrane Central Register of Controlled Trials (CENTRAL) in the Cochrane Library, MEDLINE (OVID), Embase (OVID), CINAHL (EBSCO) and Web of Science (Thomson Reuters). LILACS (Latin American and Caribbean Health Sciences Literature) was last searched in September 2016. We also contacted experts to identify eligible studies. We applied no language restrictions. SELECTION CRITERIA: Randomised controlled trials in people with suspected or proven AMI (ST-segment elevation myocardial infarction (STEMI) or non-STEMI) within 24 hours after onset, in which the intervention was inhaled oxygen (at normal pressure) compared to air, regardless of co-therapies provided to participants in both arms of the trial. DATA COLLECTION AND ANALYSIS: Two authors independently reviewed the titles and abstracts of identified studies to see if they met the inclusion criteria and independently undertook the data extraction. We assessed the quality of studies and the risk of bias according to guidance in the Cochrane Handbook for Systematic Reviews of Interventions. The primary outcome was death. The measure of effect used was the risk ratio (RR) with a 95% confidence interval (CI). We used the GRADE approach to evaluate the quality of the evidence and the GRADE profiler (GRADEpro) to import data from Review Manager 5 and create 'Summary of findings' tables. MAIN RESULTS: The updated search yielded one new trial, for a total of five included studies involving 1173 participants, 32 of whom died. The pooled risk ratio (RR) of all-cause mortality in the intention-to-treat analysis was 0.99 (95% CI 0.50 to 1.95; 4 studies, N = 1123; I2 = 46%; quality of evidence: very low) and 1.02 (95% CI 0.52 to 1.98; 4 studies, N = 871; I2 = 49%; quality of evidence: very low) when only analysing participants with confirmed AMI. One trial measured pain directly, and two others measured it by opiate usage. The trial showed no effect, with a pooled RR of 0.97 for the use of opiates (95% CI 0.78 to 1.20; 2 studies, N = 250). The result on mortality and pain are inconclusive. There is no clear effect for oxygen on infarct size (the evidence is inconsistent and low quality). AUTHORS' CONCLUSIONS: There is no evidence from randomised controlled trials to support the routine use of inhaled oxygen in people with AMI, and we cannot rule out a harmful effect. Given the uncertainty surrounding the effect of oxygen therapy on all-cause mortality and on other outcomes critical for clinical decision, well-conducted, high quality randomised controlled trials are urgently required to inform guidelines in order to give definitive recommendations about the routine use of oxygen in AMI.

Estimating the accuracy of muscle response testing: two randomised-order blinded studies.

BACKGROUND: Manual muscle testing (MMT) is a non-invasive assessment tool used by a variety of health care providers to evaluate neuromusculoskeletal integrity, and muscular strength in particular. In one form of MMT called muscle response testing (MRT), muscles are said to be tested, not to evaluate muscular strength, but neural control. One established, but insufficiently validated, application of MRT is to assess a patient's response to semantic stimuli (e.g. spoken lies) during a therapy session. Our primary aim was to estimate the accuracy of MRT to distinguish false from true spoken statements, in randomised and blinded experiments. A secondary aim was to compare MRT accuracy to the accuracy when practitioners used only their intuition to differentiate false from true spoken statements. METHODS: Two prospective studies of diagnostic test accuracy using MRT to detect lies are presented. A true positive MRT test was one that resulted in a subjective weakening of the muscle following a lie, and a true negative was one that did not result in a subjective weakening of the muscle following a truth. Experiment 2 replicated Experiment 1 using a simplified methodology. In Experiment 1, 48 practitioners were paired with 48 MRT-naïve test patients, forming unique practitioner-test patient pairs. Practitioners were enrolled with any amount of MRT experience. In Experiment 2, 20 unique pairs were enrolled, with test patients being a mix of MRT-naïve and not-MRT-naïve. The primary index test was MRT. A secondary index test was also enacted in which the practitioners made intuitive guesses ("intuition"), without using MRT. The actual verity of the spoken statement was compared to the outcome of both index tests (MRT and Intuition) and their mean overall fractions correct were calculated and reported as mean accuracies. RESULTS: In Experiment 1, MRT accuracy, 0.659 (95% CI 0.623 - 0.695), was found to be significantly different (p < 0.01) from intuition accuracy, 0.474 (95% CI 0.449 - 0.500), and also from the likelihood of chance (0.500; p < 0.01). Experiment 2 replicated the findings of Experiment 1. Testing for various factors that may have influenced MRT accuracy failed to detect any correlations. CONCLUSIONS: MRT has repeatedly demonstrated significant accuracy for distinguishing lies from truths, compared to both intuition and chance. The primary limitation of this study is its lack of generalisability to other applications of MRT and to MMT. STUDY REGISTRATION: The Australian New Zealand Clinical Trials Registry (ANZCTR; www.anzctr.org.au ; ID # ACTRN12609000455268 , and US-based ClinicalTrials.gov (ID # NCT01066312 ).

Colchicine for children with pericarditis: systematic review of clinical studies.

OBJECTIVE: To review the evidence for the efficacy and safety of colchicine in children with pericarditis. DESIGN: Systematic review. SEARCH STRATEGY: The following databases were searched for studies about colchicine in children with pericarditis (June 2015): Cochrane Central, Medline, EMBASE and LILACS. ELIGIBILITY CRITERIA: All observational and experimental studies on humans with any length of follow-up and no limitations on language or publication status were included. The outcomes studied were recurrences of pericarditis and adverse events. DATA EXTRACTION: Two authors extracted data and assessed quality of included studies using the Cochrane risk of bias tool for non-randomised trials. RESULTS: Two case series and nine case reports reported the use of colchicine in a total of 86 children with pericarditis. Five articles including 74 paediatric patients were in favour of colchicine in preventing further pericarditis recurrences. Six studies including 12 patients showed that colchicine did not prevent recurrences of pericarditis. LIMITATIONS: No randomised controlled trials (RCTs) were found. CONCLUSIONS: Although colchicine is an established treatment for pericarditis in adults, it is not routinely used in children. There is not enough evidence to support or discourage the use of colchicine in children with pericarditis. Further research in the form of large double-blind RCTs is needed to establish the efficacy of colchicine in children with pericarditis.

Design Characteristics Influence Performance of Clinical Prediction Rules in Validation: A Meta-Epidemiological Study.

BACKGROUND: Many new clinical prediction rules are derived and validated. But the design and reporting quality of clinical prediction research has been less than optimal. We aimed to assess whether design characteristics of validation studies were associated with the overestimation of clinical prediction rules' performance. We also aimed to evaluate whether validation studies clearly reported important methodological characteristics. METHODS: Electronic databases were searched for systematic reviews of clinical prediction rule studies published between 2006 and 2010. Data were extracted from the eligible validation studies included in the systematic reviews. A meta-analytic meta-epidemiological approach was used to assess the influence of design characteristics on predictive performance. From each validation study, it was assessed whether 7 design and 7 reporting characteristics were properly described. RESULTS: A total of 287 validation studies of clinical prediction rule were collected from 15 systematic reviews (31 meta-analyses). Validation studies using case-control design produced a summary diagnostic odds ratio (DOR) 2.2 times (95% CI: 1.2-4.3) larger than validation studies using cohort design and unclear design. When differential verification was used, the summary DOR was overestimated by twofold (95% CI: 1.2 -3.1) compared to complete, partial and unclear verification. The summary RDOR of validation studies with inadequate sample size was 1.9 (95% CI: 1.2 -3.1) compared to studies with adequate sample size. Study site, reliability, and clinical prediction rule was adequately described in 10.1%, 9.4%, and 7.0% of validation studies respectively. CONCLUSION: Validation studies with design shortcomings may overestimate the performance of clinical prediction rules. The quality of reporting among studies validating clinical prediction rules needs to be improved.

A European multi-language initiative to make the general population aware of independent clinical research: the European Communication on Research Awareness Need project.

BACKGROUND: The ECRAN (European Communication on Research Awareness Needs) project was initiated in 2012, with support from the European Commission, to improve public knowledge about the importance of independent, multinational, clinical trials in Europe. METHODS: Participants in the ECRAN consortium included clinicians and methodologists directly involved in clinical trials; researchers working in partnership with the public and patients; representatives of patients; and experts in science communication. We searched for, and evaluated, relevant existing materials and developed additional materials and tools, making them freely available under a Creative Commons licence. RESULTS: The principal communication materials developed were: 1. A website ( http://ecranproject.eu ) in six languages, including a Media centre section to help journalists to disseminate information about the ECRAN project 2. An animated film about clinical trials, dubbed in the 23 official languages of the European Community, and an interactive tutorial 3. An inventory of resources, available in 23 languages, searchable by topic, author, and media type 4. Two educational games for young people, developed in six languages 5. Testing Treatments interactive in a dozen languages, including five official European Community languages 6. An interactive tutorial slide presentation testing viewers' knowledge about clinical trials CONCLUSIONS: Over a 2-year project, our multidisciplinary and multinational consortium was able to produce, and make freely available in many languages, new materials to promote public knowledge about the importance of independent and international clinical trials. Sustained funding for the ECRAN information platform could help to promote successful recruitment to independent clinical trials supported through the European Clinical Research Infrastructure Network.

Does evidence-based practice improve patient outcomes? An analysis of a natural experiment in a Spanish hospital.

RATIONALE, AIMS AND OBJECTIVES: Evidence-based practice (EBP) is widely promoted, but does EBP produce better patient outcomes? We report a natural experiment when part of the internal medicine service in a hospital was reorganized in 2003 to form an EBP unit, the rest of the service remaining unchanged. The units attended similar patients until 2012 permitting comparisons of outcomes and activity. METHODS: We used routinely collected statistics (2004-11) to compare the two different methods of practice and test whether patients being seen by the EBP unit differed from standard practice (SP) patients. Data were available by doctor and year. To check for differences between the EBP and SP doctors prior to reorganization, we used statistics from 2000 to 2003. We looked for changes in patient outcomes or activity following reorganization and whether the EBP unit was achieving significantly different results from SP. Data across the periods were combined and tested using Mann-Whitney test. RESULTS: No statistically significant differences in outcomes were detected between the EBP and the SP doctors prior to reorganization. Following the unit's establishment, the mortality of patients being treated by EBP doctors compared with their previous performance dropped from 7.4% to 6.3% (P < 0.02) and length of stay from 9.15 to 6.01 days (P = 0.002). No statistically significant improvements were seen in SP physicians' performance. No differences in the proportion of patients admitted or their complexity between the services were detected. Despite this, EBP patients had a clinically significantly lower risk of death 6.27% versus 7.75% (P < 0.001) and a shorter length of stay 6.01 versus 8.46 days (P < 0.001) than SP patients. Readmission rates were similar: 14.4% (EBP); 14.5% (SP). EBP doctors attended twice as many patients/doctor as SP doctors. CONCLUSION: The EBP unit was associated with better patient outcomes and more efficient performance than achieved by the same physicians previously or by SP concurrently.

Increased water intake to reduce headache: learning from a critical appraisal.

CLINICAL BOTTOM LINE: Water intake is a cost effective, non-invasive and low-risk intervention to reduce or prevent headache pain. RATIONALE: Chronic mild dehydration may trigger headache. Increased water intake could help. A small trial shows modest benefit; however, a larger methodologically sound randomized controlled trial is needed to confirm efficacy. CRITICALLY APPRAISED PAPER: Spigt, M., Weerkamp, N., Troost, J., van Schayck, C. P., & Knottnerus, J. A. (2012). 'A randomized trial on the effects of regular water intake in patients with recurrent headaches.' Family practice, 29(4), 370-5. Doi: 10.1093/fampra/cmr112 CLINICAL SCENARIO: Patients from primary care registered as 'headache', 'tension headache' and/or 'migraine' for more than one year who suffer at least two episodes of moderately intense headache or more than four mildly intense episodes of headache per month with a daily fluid intake of less than 2.5 litres per day. PICO (M): Patient/Problem = Headache > 1 year with 2 moderately intense or 4 mildly intense episodes per month Intervention = 1.5 litres water per day + stress control and sleep hygiene Comparison/Control = stress control and sleep hygiene Outcome = Reduce or eliminate headache Methodology = Therapy RCT Table 1: Final Search Terms TRIP Data Base: hits = 517 used filter Extended Primary research 4 found 1 paper applicable 'Water intake '[MeSH Terms] AND 'Headache '[All Fields]' Best match to PICO, (2012) RCT SELECTION CRITERION AND OVERALL RESULTS: 102 headache patients in16 primary care clinics were randomized into control (n = 50) and intervention groups (n = 52) Inclusion criteria = two > episodes of moderately intense headache or five > mildly intense headaches per month and total fluid intake > 2.5 litres per day, Follow-up @ 3 months. 79% intervention and 66% of controls completed RCT. Drinking more water resulted in a statistically significant improvement of 4.5 (confidence interval: 1.3-7.8) points on Migraine-Specific Quality of Life (MSQOL). 47% in the intervention (water) group self-reported improvement (6 > on a 10-point scale) against 25% in controls. Drinking water did not reduce headache days. COMMENTS: The transparency from the author of this critically appraised paper enables others to use this study as a teaching tool and to learn from the shortcomings in the trial. The study was underpowered and contains methodological shortcomings. Participants were partially un-blinded during the trial increasing the risk for bias. Only the subjective measures are statistically significant and attrition was significant. The intervention is low risk and of negligible cost. A methodologically sound RCT is recommended to evaluate if the intervention has beneficial effects.